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      Neuroprotective Strategies after Neonatal Hypoxic Ischemic Encephalopathy

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          Abstract

          Neonatal hypoxic ischemic encephalopathy (HIE) is a devastating disease that primarily causes neuronal and white matter injury and is among the leading cause of death among infants. Currently there are no well-established treatments; thus, it is important to understand the pathophysiology of the disease and elucidate complications that are creating a gap between basic science and clinical translation. In the development of neuroprotective strategies and translation of experimental results in HIE, there are many limitations and challenges to master based on an appropriate study design, drug delivery properties, dosage, and use in neonates. We will identify understudied targets after HIE, as well as neuroprotective molecules that bring hope to future treatments such as melatonin, topiramate, xenon, interferon-beta, stem cell transplantation. This review will also discuss some of the most recent trials being conducted in the clinical setting and evaluate what directions are needed in the future.

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          JNK signaling in apoptosis.

          Jun N-terminal kinases or JNKs play a critical role in death receptor-initiated extrinsic as well as mitochondrial intrinsic apoptotic pathways. JNKs activate apoptotic signaling by the upregulation of pro-apoptotic genes through the transactivation of specific transcription factors or by directly modulating the activities of mitochondrial pro- and antiapoptotic proteins through distinct phosphorylation events. This review analyses our present understanding of the role of JNK in apoptotic signaling and the various mechanisms by which JNK promotes apoptosis.
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            Hypoxic-ischemic encephalopathy: a review for the clinician.

            Hypoxic-ischemic encephalopathy (HIE) occurs in 1 to 8 per 1000 live births in developed countries. Historically, the clinician has had little to offer neonates with HIE other than systemic supportive care. Recently, the neuroprotective therapy of hypothermia has emerged as the standard of care, and other complementary therapies are rapidly transitioning from the basic science to clinical care.
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              Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival.

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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                15 September 2015
                September 2015
                : 16
                : 9
                : 22368-22401
                Affiliations
                [1 ]Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA; E-Mails: bjdixon@ 123456llu.edu (B.J.D.); reis.cesar.llu@ 123456gmail.com (C.R.); wingiho@ 123456googlemail.com (W.M.H.); Jtang@ 123456llu.edu (J.T.)
                [2 ]Department of Anesthesiology, Loma Linda University Medical Center, Loma Linda, CA 92354, USA
                [3 ]Department of Neurosurgery, Medical University Innsbruck, Tyrol 6020, Austria
                [4 ]Department of Neurosurgery, Loma Linda University School of Medicine, Loma Linda, CA 92354, USA
                Author notes
                [†]

                These authors contributed equally to this work.

                [* ]Author to whom correspondence should be addressed; E-Mail: johnhzhang3910@ 123456yahoo.com ; Tel.: +1-909-558-4000 (ext. 44723).
                Article
                ijms-16-22368
                10.3390/ijms160922368
                4613313
                26389893
                fe788e77-0704-49d5-9e12-06ee1ff0c382
                © 2015 by the authors; licensee MDPI, Basel, Switzerland.

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 14 July 2015
                : 06 September 2015
                Categories
                Review

                Molecular biology
                neonatal hypoxic ischemic encephalopathy,neuroprotection,intervention strategy,therapeutic strategy

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